The present invention relates to a procedure as defined and to a measuring apparatus for non-invasive determination of fractional oxygen saturation in blood. Moreover, the invention relates to a sensor, designed for use in conjunction with the measuring apparatus of the invention to collect measurement data about the patient.
Specifically, the present invention relates to the monitoring of the oxygenation level of the body in patient monitoring systems. Measuring the oxygen saturation of arterial blood in peripheral circulation is generally sufficient to determine the oxygenation situation and sufficiency of oxygen supply in the entire body. The oxygenation level of the human body can be estimated via oxygen saturation measurement of arterial blood either in a non-invasive manner using pulse oximeters or transcutaneous oximeters/blood gas analysers or in an invasive manner either by taking a sample of arterial blood and analysing in vitro blood gases (In Vitro Blood Gas/pH Analyzers) or performing an optic measurement on the blood sample using so-called CO-oximeters or haemoximeters (In Vitro Multiwavelength Oximeters).
Partial pressure measurements of gas in arterial blood samples and optic methods based on the absorption of light by blood samples are part of long-standing tradition, but clinical use of pulse oximeters only became common in late 1980's and the measuring principle itself is relatively new. There are numerous patents and patent applications relating to pulse oximeters. The most important of these as well as the most comprehensive general descriptions of prior art are found in patent specifications U.S. Pat. No. 4,653,498, U.S. Pat. No. 4,819,752, U.S. Pat. No. 4,407,290 and U.S. Pat. No. 4,832,484.
The prior-art technology described in the above-mentioned patent specifications, which is the basis of currently used equipment, is imperfect and inadequate for continuous and non-invasive monitoring of changes in the actual oxygenation level or degree of fractional oxygen saturation in a patient's blood. Although in vitro oximeters are in principle capable of measuring fractional oxygen saturation from a normal blood sample, the measurement is neither non-invasive nor continuous. On the other hand, pulse oximeters measure continuously and non-invasively, but they are not able to measure the actual degree of fractional oxygen saturation of blood and are therefore inadequate for situations where only a part of the total amount of haemoglobin in a patient is functional. Pulse oximeters measure fractional oxygen saturation assuming that the patient's blood composition is the same as that of a healthy, non-smoking person. A high dyshaemoglobin level, i.e. a high relative amount of haemoglobin not participating in oxygen transport, always involves a danger to the patient because current pulse oximeters produce an incorrect estimate of the oxygenation level of blood.
The cause of incorrect measurement lies in the measuring principle: Since pulse oximeters use only two different wavelengths of light for the estimation of oxygen saturation, only two different kinds of blood haemoglobin, viz. oxyhaemoglobin (HbO2) and deoxyhaemoglobin (Hb), can be accurately measured by this method. All other dyeing blood components (usually dyshaemoglobins or dyes used in clinical tests) have a disturbing effect on the measurement and can only be taken into account as average amounts. This type of average correction is generally made on the composition of healthy blood. However, the composition of normal blood may change in an unforeseen manner and without a readily identifiable cause. The blood composition of a patient with a critical illness may differ from the blood composition of a healthy person as a result of medication, the nature of the illness or a medical treatment or measurement. A new and significant treatment of this type is the so-called nitrogen oxide (NO) treatment, which may cause a considerable rise in the patient's methaemoglobin (MetHb) level. Another common case of incorrect measurement is carbon monoxide poisoning, which involves a high carboxyhaemoglobin (HbCO) level in the patient. Continuous non-invasive monitoring of the actual degree of oxygen saturation is particularly important during NO treatment because the dyshaemoglobin levels may rise relatively rapidly, which means that an analysis based on a blood sample is not sufficient. The measurement of fractional oxygen saturation is also of great importance in rescue operations and in follow-up monitoring after carboxyhaemoglobin poisoning.
It is obvious that accurate, continuous and non-invasive measurement of fractional oxygen saturation requires a sensor with several wavelengths used to produce an analysis of blood composition. In the following, prior art will be discussed by considering a technique that uses the principle of non-invasive measurement using an oximeter with several wavelengths.
A previously known oximeter based on non-invasive measurement uses eight different wavelengths to determine the average degree of oxygenation of the blood via a measurement on the ear (see Girsh et Girsh, Ann. Allergy, 42, pages 14-18, 1979). The measurement does not use the pulse oximeter principle, whereby the measurement is only applied to arterial blood by distinguishing from the light transmission a component pulsating in synchronism with the heartbeat and normalising this component against the total light transmission. Instead, average oxygen saturation is measured directly from the total light transmission at the wavelengths used. The total transmission depends on the oxygen saturation and composition of both arterial and venous blood, but also on the absorption and scattering caused by other tissues. Typically, blood accounts for only 1-2% of the amount of tissue, so the signal may be very ambiguous. Such a method has many drawbacks: First, the person's complexion, the structure of the tissue in itself and especially the scattering and absorption properties of the tissue as well as its other properties change and even dominate the total transmission. In fact, the method requires several wavelengths for the compensation of these properties, and it cannot produce reliable analyses of the composition of arterial blood. In addition, analysing the blood composition in terms of percentages is difficult because the relative amounts of arterial blood and venous blood and their different degrees of oxygen saturation affect the absorption. The amount of dyshaemoglobins is the same in both arteries and veins, but oxygen saturation varies with tissue metabolism and temperature or with the regulating mechanisms of the body.
In patents EP 335357 and U.S. Pat. No. 5,421,329 it is suggested that by adding a third wavelength to a conventional pulse oximeter with two wavelengths it is possible to improve the accuracy of functional saturation measurement with a pulse oximeter or to eliminate or reduce the artifacts caused e.g. by movement. In the former patent, the third wavelength is used to eliminate the irregular artifacts signal from on top of the pulsation caused by the heartbeat. The wavelength is not used for the determination or identification of the dyshaemoglobin level. In the latter patent, the third wavelength is used to adjust the measurement of a low degree of oxygen saturation, but it is not used in conjunction with the measurement of the normal saturation range or for the measurement of dyshaemoglobin levels or the degree of fractional oxygen saturation. The latter patent also relates to the reflection principle and especially to the measurement of oxygen saturation in a baby during childbirth. In this situation, a third wavelength is naturally needed to achieve a more reliable measurement. Similarly, patent application WO 94/03102 proposes the use of a third wavelength to eliminate artifacts caused by motion. Patent specification U.S. Pat. No. 4,714,341 (Minolta Camera) also uses a third wavelength for more accurate measurement of functional saturation. Like the others, this specification is not concerned with the measurement of fractional saturation or in general dyshaemoglobin levels.
Patent specification EP 0 524 083 also proposes the use of a third wavelength for simultaneous measurement of carboxyhaemoglobin level and oxygen saturation. In the measurement, three different laser diodes with wavelengths of 660 nm, 750 nm and 960 nm are used. These three wavelengths are used to measure the modulation ratios, and the concentrations of three unknown kinds of haemoglobin, HbO2, Hb and HbCO, are calculated by solving a linear system of equations. However, the procedure presented in patent specification EP 0 524 083 has two significant drawbacks. First, the procedure is not applicable for the measurement of MetHb; in other words, fractional saturation can only be determined for the three kinds of Hb mentioned above. Secondly, solving the aforesaid linear system of equations is not sufficient for the determination of the concentrations of the aforesaid three kinds of Hb, as will become evident later on from the description of a preferred embodiment of the calculating procedure of the present invention. The basic drawback is that the system of equations is not a linear one because the coefficients used in it are in themselves functions of the concentrations. For this reason, the use of this method is restricted to a very narrow range of oxygen saturation, and the procedure is not workable in the operating range generally required for pulse oximeters. In addition to the above drawbacks, the procedure involves the use of laser diodes and a fibre optic connection to the measurement point, which makes the measuring system rather too expensive for practical measurements and difficult for the user. Moreover, laser diodes have a narrow choice of wavelengths. Due to the use of fibre optics, the light is attenuated especially at the connection points and the signal-to-noise ratio is worse than in the conventional solution employing light-emitting diodes. The official regulations relating to coherent radiation and the danger caused by the radiation e.g. to the eye also constitute a limitation of the application of the procedure in practical situations.
Further, patent specification Aoyagi et al, EP 0 679 890 A1, representing prior art, presents an apparatus designed for the measurement of light absorbing blood components. According to the specification, the procedure and apparatus can be used to determine the degree of functional oxygen saturation of blood, the concentrations of different kinds of haemoglobin as well as other dye components of blood, such as bilirubin and in-vein dyes. The proposed procedure and apparatus are based on a rather unusual optical model of light transmission through tissue and formation of a pulsating signal. Since the procedure is obviously one of the prior-art solutions related to the present invention, it is necessary to point out the erroneous assumptions lying behind the procedure and apparatus. The drawbacks listed below serve as examples, and the drawbacks are not described in full extent. For a more detailed explanation of the drawbacks, reference is made to the thesis Reindert Graaff, "Tissue Optics Applied to Reflectance Pulse Oximetry", Groningen University, Feb. 12, 1993, which is an excellent description of tissue optics and its modern representation. To those familiar with pulse oximetry or non-invasive measurement of blood properties, the drawbacks listed below are self-evident and can be recognised via empirical measurements. Accordingly, patent application EP 0 679 890 is based on the following, erroneous propositions. First, diffusion approximation and its parametrised flux models (in the application referred to, the so-called Arthur Schuster theory) can be applied to describe the total transmission through tissue, but they cannot be used in conjunction with pulsating tissue components and the operation of pulse oximeters at short wavelengths (600-700 nm), nor can they generally be used at a low saturation or for highly absorptive blood dye components. Using the diffusion model (applies to situations where the scattering cross-section is considerably larger than the absorption cross-section) together with the Lambert-Beer pulse oximeter model (applies to situations where the absorption cross-section is considerably larger than the scattering cross-section) simultaneously generally does not lead to realistic results. Second, it is stated in the patent application that the scattering term is known and independent of the wavelength. In fact, the scattering term is one of the adjustable parameters in the model and is also dependent on the wavelength and the tissue type. The pulsating portion of the scattering is also dependent on the size, shape and number of blood cells, i.e. on the haematocrit. Third, the tissue term (in the patent application, the pulsating component that is not blood) plays no significant role in the signal formation at all and therefore it cannot be used in the way it appears in the formulas as a factor representing theoretical extinction coefficients of blood and empirically measured modulation ratios. Further, it is stated in the patent application that the tissue term is mostly water, which in fact does not absorb at all in relation to the dominating pulsating terms in the wavelength range used. In fact, the dominating pulsating tissue-type effect is produced by blood, whose absorption depends on all those things that patent application EP 0 679 890 presents as quantities to be measured, such as oxygen saturation, different haemoglobin varieties and their amounts and dyes; thus, there would be no linear correlation between different tissue terms that could be defined in advance--although the application asserts to the contrary--which means that the degree of non-linearity of the problem increases considerably. Fifth, the number of unknown quantities in the procedure and apparatus of the patent application in question clearly exceeds the number of equations available. Moreover, the patent application contains numerous other inaccuracies, so the application or the procedure and apparatus presented in it do not, at least in respect of their basic assumptions, meet the quality criteria that are expected to be observed in clinical patient monitoring measurements.
In the above, existing prior art has been dealt with from the point of view of systems using more than two different light sources each having a different spectral emission, yet so that the spectral emission in the same light source is always the same. Especially the use of more than two light sources is still associated with problems relating to maintaining the accuracy of the apparatus in use even in situations where the spectral emission of the light sources changes due to technical aspects of fabrication of the light source and maintaining accuracy requires a correction to compensate this change. A method for such correction or rather a cheap method for maintaining sensor accuracy is presented in U.S. Pat. No. 4,621,643 (December 1986), U.S. Pat. No. 4,700,708 (October 1987) and U.S. Pat. No. 4,770,179 (September 1988). All these patents propose solutions in which information about the wavelengths of the light sources is transmitted to the measuring apparatus by encoding the correction required by changes of wavelength into an impedance element or in practice into the resistance value of a resistor. From the resistance value or by some other similar coding method, the measuring apparatus receives information indicating the changes required in the calibration of the apparatus. This can be done with a single resistance value or other simple `coding` when the unambiguity of the measurement signal is guaranteed via other techniques. In two-wavelength pulse oximeters, unambiguity is based on the apparatus forming substantially only one signal, i.e. a modulation ratio between the two wavelengths, a so-called R-value, which, via an unambiguous calibration curve, can be directly associated with the functional oxygen saturation or SpO2 value. No such unambiguous correlation exists when there are several light sources and more than two haemoglobin varieties or other blood dye components are to be measured. As a summary of prior art, it can be stated that so far there is no method or apparatus capable of reliable measurement of fractional oxygen saturation of arterial blood and quantitative determination of the dyshaemoglobin level.